Pyles J M, March K L, Franklin M, Mehdi K, Wilensky R L, Adam L P
Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, USA.
Circ Res. 1997 Dec;81(6):904-10. doi: 10.1161/01.res.81.6.904.
Vascular restenosis involves contraction, proliferation, and remodeling of the arterial wall in response to overstretch injury. Mitogen-activated protein kinases (MAPKs) are implicated in both contraction and proliferation of vascular smooth muscle (VSM), and studies of porcine carotid arterial muscle strips have shown that mechanical stretch leads to the activation of the extracellular signal-regulated kinase (ERK) family of MAPKs in vivo. We, therefore, analyzed the acute effect of mechanical overstretch injury on ERK-MAPK (herein referred to simply as MAPK) activity in porcine coronary and carotid arteries in vivo. Balloon angioplasty catheters were inflated to 6 atm three times over 5 minutes at a balloon-artery ratio of 1.2:1 in either porcine coronary or carotid arteries. The arteries were snap-frozen after angioplasty, and MAPK activity was measured. Angioplasty of the left anterior descending (LAD, n = 5), left circumflex (LCx, n = 5), and carotid (n = 5) arteries effected an increase in MAPK activity compared with the activity in uninstrumented right coronary arteries (RCAs) or carotid arteries from the same animals used for controls. Balloon angioplasty of carotid arteries led to an increase in MAPK activity that was 7.7-fold over the activity in control arteries and comparable to the activity in stretched carotid arterial muscle strips in vivo. The increase in coronary artery kinase activity on angioplasty was variable from animal to animal. The increase in MAPK activity over that in control arteries ranged from 4.5- to 31.7-fold (mean +/- SEM, 10.7 +/- 5.3) in the LAD and 1.8- to 31.3-fold (mean +/- SEM, 9.7 +/- 5.7) in the LCx. There were no apparent inherent differences in the levels of MAPK activity in the three different types of coronary arteries (RCA, LAD, and LCx) without instrumentation. MAPK activation occurs rapidly during angioplasty, suggesting that this kinase may play an early role in initiating the injury response in both porcine coronary and carotid arteries. MAPKs may be key enzymes targeted to treat or prevent restenosis.
血管再狭窄涉及动脉壁因过度伸展损伤而发生的收缩、增殖和重塑。丝裂原活化蛋白激酶（MAPK）与血管平滑肌（VSM）的收缩和增殖均有关，对猪颈动脉肌条的研究表明，机械性伸展可导致体内细胞外信号调节激酶（ERK）家族的MAPK激活。因此，我们分析了机械性过度伸展损伤对猪冠状动脉和颈动脉体内ERK-MAPK（本文简称为MAPK）活性的急性影响。在猪冠状动脉或颈动脉中，以1.2:1的球囊-动脉比例，在5分钟内将球囊血管成形术导管充气至6个大气压3次。血管成形术后将动脉迅速冷冻，并测量MAPK活性。与未进行操作的同一动物的右冠状动脉（RCA）或颈动脉中的活性相比，左前降支（LAD，n = 5）、左旋支（LCx，n = 5）和颈动脉（n = 5）的血管成形术使MAPK活性增加。颈动脉的球囊血管成形术导致MAPK活性增加，比对照动脉中的活性高7.7倍，与体内拉伸的颈动脉肌条中的活性相当。血管成形术后冠状动脉激酶活性的增加在不同动物之间有所不同。与对照动脉相比，LAD中MAPK活性的增加范围为4.5至31.7倍（平均值±标准误，10.7±5.3），LCx中为1.8至31.3倍（平均值±标准误，9.7±5.7）。在未进行操作的情况下，三种不同类型的冠状动脉（RCA、LAD和LCx）中MAPK活性水平没有明显的固有差异。MAPK激活在血管成形术期间迅速发生，表明该激酶可能在启动猪冠状动脉和颈动脉的损伤反应中起早期作用。MAPK可能是用于治疗或预防再狭窄的关键酶。
